Functional evidence for the involvement of Arabidopsis IspF homolog in the nonmevalonate pathway of plastid isoprenoid biosynthesis

Planta ◽  
2005 ◽  
Vol 223 (4) ◽  
pp. 779-784 ◽  
Author(s):  
Ming-Hsiun Hsieh ◽  
Howard M. Goodman
Keyword(s):  
Isoprenoid Biosynthesis ◽  
Nonmevalonate Pathway

scholarly journals The lytB Gene of Escherichia coli Is Essential and Specifies a Product Needed for Isoprenoid Biosynthesis

2001 ◽  
Vol 183 (24) ◽  
pp. 7403-7407 ◽  
Author(s):  
Sean McAteer ◽  
Andrew Coulson ◽  
Neil McLennan ◽  
Millicent Masters
Keyword(s):  
Escherichia Coli ◽  
Protein Structure ◽  
Cell Lysis ◽  
Isoprenoid Biosynthesis ◽  
Globular Protein ◽  
Limited Growth ◽  
E Coli ◽  
Nonmevalonate Pathway ◽  
Tim Barrel

ABSTRACT LytB and GcpE, because they are codistributed with other pathway enzymes, have been predicted to catalyze unknown steps in the nonmevalonate pathway for isoprenoid biosynthesis. We constructed a conditional Escherichia coli lytB mutant and found that LytB is essential for survival and that depletion of LytB results in cell lysis, which is consistent with a role for this protein in isoprenoid biosynthesis. Alcohols which can be converted to pathway intermediates beyond the hypothesized LytB step(s) support limited growth of E. coli lytB mutants. An informatic analysis of protein structure suggested that GcpE is a globular protein of the TIM barrel class and that LytB is also a globular protein. Possible biochemical roles for LytB and GcpE are suggested.

scholarly journals Improved Efficacy of Fosmidomycin against Plasmodium and Mycobacterium Species by Combination with the Cell-Penetrating Peptide Octaarginine

2013 ◽  
Vol 57 (10) ◽  
pp. 4689-4698 ◽  
Author(s):  
Christof Sparr ◽  
Nirupam Purkayastha ◽  
Beata Kolesinska ◽  
Martin Gengenbacher ◽  
Borko Amulic ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Isoprenoid Biosynthesis ◽  
Cell Permeability ◽  
Target Cells ◽  
Intracellular Pathogens ◽  
Content Type ◽  
Chemical Genetic ◽  
Nonmevalonate Pathway ◽  
Cell Penetrating ◽  
Covalently Linked

ABSTRACTCellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. The transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (CPPs), such as oligoarginines. Here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the CPP octaarginine. Fosmidomycin is an antibiotic that inhibits the second reaction in the nonmevalonate pathway of isoprenoid biosynthesis, an essential pathway for many obligate intracellular pathogens, including mycobacteria and apicomplexan parasites. We observed a strict correlation between octaarginine host cell permeability and its ability to improve the efficacy of fosmidomycin.Plasmodium bergheiliver-stage parasites were only partially susceptible to an octaarginine-fosmidomycin complex. Similarly,Toxoplasma gondiiwas only susceptible during the brief extracellular stages. In marked contrast, a salt complex of octaarginine and fosmidomycin greatly enhanced efficacy against blood-stagePlasmodium falciparum. This complex and a covalently linked conjugate of octaarginine and fosmidomycin also reverted resistance ofMycobacteriato fosmidomycin. These findings provide chemical genetic evidence for vital roles of the nonmevalonate pathway of isoprenoid biosynthesis in a number of medically relevant pathogens. Our results warrant further investigation of octaarginine as a delivery vehicle and alternative fosmidomycin formulations for malaria and tuberculosis drug development.

Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production

2019 ◽  
Author(s):  
Sean Lund ◽  
Taylor Courtney ◽  
Gavin Williams
Keyword(s):  
Synthetic Biology ◽  
Building Blocks ◽  
Isoprenoid Biosynthesis ◽  
Thermoplasma Acidophilum ◽  
Substrate Promiscuity ◽  
Enzymatic Pathways ◽  
First Time ◽  
Rate Limiting ◽  
Alcohol Dependent ◽  
Isopentenyl Phosphate

Isoprenoids are a large class of natural products with wide-ranging applications. Synthetic biology approaches to the manufacture of isoprenoids and their new-to-nature derivatives are limited due to the provision in Nature of just two hemiterpene building blocks for isoprenoid biosynthesis. To address this limitation, artificial chemo-enzymatic pathways such as the alcohol-dependent hemiterpene pathway (ADH) serve to leverage consecutive kinases to convert exogenous alcohols to pyrophosphates that could be coupled to downstream isoprenoid biosynthesis. To be successful, each kinase in this pathway should be permissive of a broad range of substrates. For the first time, we have probed the promiscuity of the second enzyme in the ADH pathway, isopentenyl phosphate kinase from Thermoplasma acidophilum, towards a broad range of acceptor monophosphates. Subsequently, we evaluate the suitability of this enzyme to provide non-natural pyrophosphates and provide a critical first step in characterizing the rate limiting steps in the artificial ADH pathway.<br>

scholarly journals A RubisCO-like protein links SAM metabolism with isoprenoid biosynthesis

2012 ◽  
Vol 8 (11) ◽  
pp. 926-932 ◽  
Author(s):  
Tobias J Erb ◽  
Bradley S Evans ◽  
Kyuil Cho ◽  
Benjamin P Warlick ◽  
Jaya Sriram ◽  
...  
Keyword(s):  
Isoprenoid Biosynthesis

scholarly journals The Coordinated Upregulated Expression of Genes Involved in MEP, Chlorophyll, Carotenoid and Tocopherol Pathways, Mirrored the Corresponding Metabolite Contents in Rice Leaves during De-Etiolation

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1456
Author(s):  
Xin Jin ◽  
Can Baysal ◽  
Margit Drapal ◽  
Yanmin Sheng ◽  
Xin Huang ◽  
...  
Keyword(s):  
Higher Plants ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Isoprenoid Biosynthesis ◽  
Promoter Regions ◽  
Expression Of Genes ◽  
Coordinated Expression ◽  
Rice Leaves ◽  
Mechanistic Basis ◽  
Phosphate Synthase

Light is an essential regulator of many developmental processes in higher plants. We investigated the effect of 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1/2 genes (OsHDR1/2) and isopentenyl diphosphate isomerase 1/2 genes (OsIPPI1/2) on the biosynthesis of chlorophylls, carotenoids, and phytosterols in 14-day-old etiolated rice (Oyza sativa L.) leaves during de-etiolation. However, little is known about the effect of isoprenoid biosynthesis genes on the corresponding metabolites during the de-etiolation of etiolated rice leaves. The results showed that the levels of α-tocopherol were significantly increased in de-etiolated rice leaves. Similar to 1-deoxy-D-xylulose-5-phosphate synthase 3 gene (OsDXS3), both OsDXS1 and OsDXS2 genes encode functional 1-deoxy-D-xylulose-5-phosphate synthase (DXS) activities. Their expression patterns and the synthesis of chlorophyll, carotenoid, and tocopherol metabolites suggested that OsDXS1 is responsible for the biosynthesis of plastidial isoprenoids in de-etiolated rice leaves. The expression analysis of isoprenoid biosynthesis genes revealed that the coordinated expression of the MEP (2-C-methyl-D-erythritol 4-phosphate) pathway, chlorophyll, carotenoid, and tocopherol pathway genes mirrored the changes in the levels of the corresponding metabolites during de-etiolation. The underpinning mechanistic basis of coordinated light-upregulated gene expression was elucidated during the de-etiolation process, specifically the role of light-responsive cis-regulatory motifs in the promoter region of these genes. In silico promoter analysis showed that the light-responsive cis-regulatory elements presented in all the promoter regions of each light-upregulated gene, providing an important link between observed phenotype during de-etiolation and the molecular machinery controlling expression of these genes.

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